Cancer is a major public health problem. It accounts for approximately one quarter of all deaths in the United States, and is the leading cause of death among men and women under 85 years of age. The lifetime probability of developing cancer is 46% for men and 38% for women. Many anti-cancer therapies are plagued by side effects including nausea, emesis, hair loss, fever, and risk of infection. Chemotherapy and radiotherapy both lead to high rates of oral and gastrointestinal (GI) mucositis in treated patients, and these effects can be the dose-limiting toxicities of some treatment modalities.
Tumor cells acquire a high level of adaptive heat shock response. The heat shock response is an adaptive mechanism used by all living cellular organisms to survive under the conditions of so-called proteotoxic stress—the condition resulting in accumulation of misfolded proteins, which tend to aggregate leading to cell death due to global protein denaturing triggered by such aggregation. Cells can activate this protective mechanism by inducing synthesis of additional protein chaperones, known as heat shock proteins (HSP).
Tumor cell viability may be dependent on heat shock response because they have higher rate of protein misfolding. However, the efficacy of thermotherapy techniques for cancer are limited by the induction of adaptive heat shock response, which can greatly diminish tumor cell sensitivity to treatment and limit the use of thermotherapy and other heat shock modulating treatments. Accordingly, there is a need for improved methods of inducing cell death.